Center of Integrated Protein Science Munich (CIPS-M), Division of Clinical Pharmacology, Klinikum der Universität München, Munich, Germany; Department of Medicine II, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
Center of Integrated Protein Science Munich (CIPS-M), Division of Clinical Pharmacology, Klinikum der Universität München, Munich, Germany.
Pathology. 2019 Oct;51(6):586-592. doi: 10.1016/j.pathol.2019.06.001. Epub 2019 Aug 21.
Development, course of disease and prognosis of hepatocellular carcinomas (HCC) are strongly influenced by the immune system. Immunosuppressive regulatory T cells (Treg) have been shown to negatively impact disease progression and survival. To further understand the mechanisms of Treg attraction to HCC lesions, this study provides an analysis of Treg attracting chemokines in human HCC tissues. We analysed the expression of the Treg attracting chemokines CCL1 and CCL22 as well as the infiltration of FoxP3+ Treg and CD8+ T cells in paraffin-embedded tissue sections of 62 HCC patients. Expression of both chemokines was detected in 47 of 62 tissue slides. Chemokine expression was generally higher in tumour stroma and peritumoural liver tissue than in the tumour tissue itself. CD8+ T cells and FoxP3+ Treg were found at high levels in many tumour tissues. Intratumoural infiltration of Treg positively correlated with CCL22 levels in peritumoural liver tissue. In contrast, no correlation of Treg numbers and expression of CCL1 was detected. In summary, we describe here that the chemokines CCL1 and CCL22 are expressed in HCC tissues and, to a higher extent, in the stroma and peritumoural liver tissue. CCL22 may contribute to Treg recruitment and immunosuppression, whereas the role of CCL1 remains to be defined. It will be interesting to investigate the potential of these chemokines as drug targets for cancer therapy.
肝癌（HCC）的发展、病程和预后受免疫系统的强烈影响。已证实免疫抑制性调节性 T 细胞（Treg）会对疾病进展和生存产生负面影响。为了进一步了解 Treg 向 HCC 病变趋化的机制，本研究分析了人 HCC 组织中 Treg 趋化因子的表达。我们分析了 Treg 趋化因子 CCL1 和 CCL22 的表达以及 FoxP3+Treg 和 CD8+T 细胞在 62 例 HCC 患者石蜡包埋组织切片中的浸润情况。在 62 个组织切片中有 47 个检测到两种趋化因子的表达。趋化因子的表达在肿瘤基质和肿瘤周围肝组织中通常高于肿瘤组织本身。在许多肿瘤组织中，CD8+T 细胞和 FoxP3+Treg 表达水平较高。肿瘤内 Treg 的浸润与肿瘤周围肝组织中 CCL22 水平呈正相关。相比之下，未检测到 Treg 数量与 CCL1 表达之间的相关性。总之，我们在此描述了趋化因子 CCL1 和 CCL22 在 HCC 组织中表达，并且在基质和肿瘤周围肝组织中表达程度更高。CCL22 可能有助于 Treg 的募集和免疫抑制，而 CCL1 的作用仍有待确定。研究这些趋化因子作为癌症治疗药物靶点的潜力将是有趣的。
